Combination of ablative fractional carbon dioxide laser and platelet-rich plasma treatment to improve hypertrophic scars: a retrospective clinical ...
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Burns & Trauma, 2021, 9, tkab016
https://doi.org/10.1093/burnst/tkab016
Research Article
Research Article
Combination of ablative fractional carbon
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dioxide laser and platelet-rich plasma treatment
to improve hypertrophic scars: a retrospective
clinical observational study
Zhanzhan Dai1 ,2 ,† , Xiaozhen Lou1 ,2 ,† , Tuo Shen1 ,2 ,† , Yu Sun1 ,2 ,
Yongqiang Xiao1 ,3 , Xingfeng Zheng1 ,2 , Xuexin Wang1 ,2 , Yu Peng1 ,2 ,
Yukun Guo1 ,2 , Yibin Guo4 , Jiannan Wen5 , He Fang1 ,2 ,*, Bing Ma1 ,2 ,* and
Zhaofan Xia1 ,2 ,*
1
Department of Burn Surgery, the First Affiliated Hospital of Naval Medical University; Burn Institute of PLA; 168
Changhai Road, Yangpu District, Shanghai 200433, China, 2 Research Unit of key techniques for treatment of burns
and combined burns and trauma injury, Chinese Academy of Medical Sciences, 168 Changhai Road, Yangpu District,
Shanghai 200433, China, 3 Department of Burn and Plastic Surgery, the 970th Hospital of People’s Liberation Army, 7
Zhichunan Road, Zhifu District, Yantai, Shandong, 264000, China, 4 Department of Health Statistics, the Naval Medical
University, 800 Xiangyin Road, Yangpu District, Shanghai 200433, China, and 5 First Resident Outpatient Department of
Northern Theater General Hospital, 22 Beiwu Road, Heping District, Shenyang, Liaoning Province, 110001, China
*Correspondence. He Fang, Email: fanghe_2005@163.com; Bing Ma, Email: truesesmmu@163.com; Zhaofan Xia,
Email: xiazhaofan_smmu@163.com
†
Zhanzhan Dai, Xiaozhen Lou and Tuo Shen finished the main work equally.
Received 18 January 2021; Revised 20 February 2021; Accepted 16 April 2021
Abstract
Background: Hypertrophic scars are one of the main complications that affect the quality of life
of patients after burns. Many methods have been shown to be effective in the treatment of
hypertrophic scars, such as ablative fractional CO2 laser (AFCL) and platelet-rich plasma (PRP).
However, there are few studies on the effect of the combined application of these measures.
The purpose of this study was to explore the therapeutic effect of AFCL combined with PRP on
hypertrophic burn scars.
Methods: A retrospective clinical observation study was conducted on 50 patients with hyper-
trophic burn scars. The AFCL+PRP group included 31 patients who received AFCL combined
with PRP treatment; the AFCL group included 19 patients who received AFCL treatment only. The
University of North Carolina 4P Scar Scale (UNC4P) and the Vancouver Scar Scale (VSS) scores that
were collected before each treatment were used as indicators of the effectiveness of the previous
treatment. The scores recorded at the second, fourth and seventh months were analysed.
Results: The demographic data of the 2 groups were not significantly different. Before treatment,
there was no difference in the UNC4P and VSS scores between the 2 groups. There was a significant
decline in the UNC4P and VSS total scores over 6 months in both groups (p < 0.05) and scores in the
2 groups were comparable after 3 and 6 months (p < 0.05). UNC4P scores in the AFCL+PRP group
decreased from a mean of 8.26 to 2.61 (p < 0.05) with a concomitant drop in VSS scores from a
mean of 11.74 to 6.06 (p < 0.01). In the AFCL group UNC4P and VSS scores decreased from 7.68 to
4.63 (p < 0.05) and from 10.89 to 8.16 (p < 0.05), respectively. The sub-items of these 2 assessments
© The Author(s) 2021. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), 1
which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.2 Burns & Trauma, 2021, Vol. 9, tkab016
were analysed and the results suggest that AFCL combined with PRP can comprehensively improve
scarring.
Conclusions: This study shows that PRP is an effective adjunct for AFCL in the treatment of
hypertrophic burn scars and that the combination of PRP and AFCL proved to be more useful than
AFCL alone. This combination may be a new and effective clinical practice for the treatment of
scars. However, larger and higher-level clinical studies are still needed to determine its efficacy
and possible mechanisms.
Key words: Ablative fractional carbon dioxide laser, Platelet-rich plasma, Hypertrophic scars
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Highlights
• We explored the therapeutic effect of ablative fractional CO2 laser (AFCL) combined with platelet-rich plasma (PRP) on
hypertrophic scars.
• Our results suggest that AFCL combined with PRP can comprehensively improve hypertrophic scars.
• The combination of PRP and AFCL proved more useful than AFCL alone.
Background A retrospective and comparative clinical observation study
Hypertrophic scars are the main clinical result of full- was conducted on 50 burn patients with hypertrophic scars
thickness burn wounds. Their prevalence has been reported to who attended the burn centre at the hospital affiliated to the
be as high as 70% [1], independent of treatment strategy. The Naval Medical University in China during the period from
disfigurement, pain, itching and contracture deformity caused August 2017 to March 2020. Among the enrolled patients, 31
by hypertrophic scars place a large psychological burden on patients (19 men and 12 women), with a mean age of 41 years
patients and affect their quality of life [2]. The mechanism (range, 22–75), were treated with AFCL and PRP combined;
of scar formation is relatively well understood: it is mainly we termed these the AFCL+PRP group. The remaining 19
caused by the massive increase in collagen and fibre dimen- patients (8 men and 11 women), with a mean age of 40 years
sions during the repair of the damaged area [3]. Although (range 20–59), underwent AFCL only. Eligible patients had
there are many methods used in scar treatment, such as to meet the following inclusion criteria: (1) diagnosed with
physiotherapy, compression, topical drugs and surgery, these hypertrophic burn scar; (2) aged >16 years; (3) completed a
methods still have some limitations [4]. Since Hantash et al. total of 7 sessions of AFCL or AFLC+PRP treatments once
[5] first applied ablative fractional CO2 laser (AFCL) in the per month within 6 months; and (4) have complete follow-up
treatment of hypertrophic burn scars in 2007, its therapeutic and clinical information record. The exclusion criteria were as
effects have become increasingly evident [6]. Platelet-rich follows: (1) infection in the scar area; (2) pregnant or lactating
plasma (PRP) has been proven useful in many fields, especially women; (3) use of drugs or related blood diseases that affect
because it releases high concentrations of growth factors and platelet concentration or function; (4) retinoid therapy within
enhances cell proliferation and angiogenesis to promote tissue 6 months of the beginning of the study; and (5) chronic
repair and reduce scar formation [7]. Several studies have wound or scar rupture.
investigated the effect of PRP and AFCL on acne scarring.
However, there are few studies on the effect of PRP and Preparation of PRP
AFCL on hypertrophic burn scars. Therefore, we conducted The 2-step centrifugation method was used in this case series
the present study to explore the effects of PRP combined with as follows. Before the treatment, 10 ml of venous blood
AFCL in patients with hypertrophic scars. was drawn from the patient’s peripheral access into a blood
collection tube containing sodium citrate as an anticoagu-
lant and transferred to a centrifuge (PRP preparation kits,
Methods Shandong Weigao Group Medical Polymer Company Ltd,
Study setting China). After centrifugation at 2750 revolutions per minute
This retrospective controlled study met the basic require- for 10 minutes, the blood sample was separated into 3 layers.
ments of the Helsinki Declaration. According to the policy Using a needle, the lowest layer, containing red blood cells,
of the Ethics Committee of the First Affiliated Hospital of was extracted and the remaining parts were centrifuged again
Naval Medical University, clinical data can be analysed and at 2750 revolutions per minute for 5 minutes. After removing
used without revealing the identity of the patient. the upper layer, PRP was separated out.
Ethical approval and consent were obtained from Shang-
hai Changhai Hospital Ethics Committee (CHEC2014-096) Treatment protocol
for the data in this research. And the patient’s clinical data Different anaesthetic methods were applied according to the
can be used for research purposes. size of the scar: general anaesthesia or spinal anaesthesiaBurns & Trauma, 2021, Vol. 9, tkab016 3
Table 1. Demographic characteristics of hypertrophic scar patients
Variables AFCL (n = 19) AFCL+PRP (n = 31) Statistical variables P value
Male, n(%) 8 (42.1%) 19 (61.3%) χ 2 = 1.746 0.186
Age, years (mean ± SD) 40 ± 10.31 41 ± 12.70 t = 0.409 0.685
BMI 23.08 ± 2.51 22.84 ± 3.01 t = 0.279 0.781
TBSA of burn, % (mean ± SD) 48.00 ± 26.49 37.58 ± 28.24 t = 1.290 0.203
Skin graft, n(%) 10 (52.6%) 15 (48.4%) χ 2 = 0.005 0.944
AFCL ablative fractional CO2 laser, PRP platelet-rich plasma, BMI body mass index, TBSA total body surface area
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for large scars (>20% total body surface area (TBSA)) and There were no significant differences between the intraoper-
local anaesthesia with compound lidocaine cream for smaller ative analgesic regimens with respect to sex, age, body mass
scars (≤20% TBSA). After anaesthesia, the treatment area index or TBSA of burn between the 2 groups (Table 1).
was sterilized with chlorhexidine before each treatment pro-
cedure. The patients underwent 10,600 nm fractional CO2
laser exposures (Ultralise Encore, Lumennis Co. Ltd, China)
Comparing the improvement between AFCL and
for the whole scar, using the deep tissue handpiece with an
AFCL+PRP groups
energy of 17.5–100 mJ, a density of 3–5% and a frequency
Before treatment, the UNC4P (7.68 ± 1.17 vs 8.26 ± 1.22)
of 250 Hz. Wound care after laser therapy included appli-
and VSS (10.89 ± 1.65 vs 11.74 ± 1.61) scores were not
cation of Prontosan gel (B. Braun Medical AG, Germany)
significantly different between the AFCL and AFCL+PRP
and changing the external dressing 5–10 days after each
groups. The sub-items of both scales also showed no statis-
AFCL operation. For the AFCL+PRP group, the PRP was
tically significant differences (Table 2).
spread evenly onto the wounds following AFCL operations.
In the AFCL group, the scores from both scales decreased
Appropriate wound dressings were used to cover the treated
after treatment compared with before treatment. The UNC4P
areas for 7 days following laser treatment. Sessions were
scores after 1, 3 and 6 months were 6.84 ± 1.27, 5.95 ± 0.55
conducted every month for 6 consecutive sessions.
and 4.63 ± 1.09, respectively; the scores after 3 and 6 months
were significantly lower than those before treatment
Data collection and outcome measures (p < 0.05; Figure 1). The VSS scores after 1, 3 and 6 months
All cases were evaluated by 2 blinded dermatologists using were 10.68 ± 1.66, 9.89 ± 1.62 and 8.16 ± 1.93, respectively;
the University of North Carolina 4P Scar Scale (UNC4P) the scores after 3 and 6 months were significantly lower
and the Vancouver Scar Scale (VSS) before every session and than those before treatment (p < 0.05; Figure 2). This
1 month after the last session. The UNC4P scale includes suggests that AFCL plays a positive role in improving scar
pliability, pruritus, pain and paraesthesia. The VSS includes formation.
pigmentation, vascularity, height and pliability. Assessment In the AFCL+PRP group, the UNC4P and VSS scores
was documented before every session and 1 month after the improved similarly. After 1, 3 and 6 months of treatment,
final session. the UNC4P scores were 6.52 ± 1.16, 4.68 ± 1.28 and
2.61 ± 1.29, respectively; the scores after 3 and 6 months
were significantly lower than those before treatment
Statistical analysis (p < 0.05; Figure 1). The VSS scores were 10.39 ± 1.31,
The collected data were revised, tabulated and analysed 8.45 ± 1.04 and 6.06 ± 1.44, respectively, after 1, 3 and
using IBM SPSS version 24 software (IBM SPSS, Chicago, 6 months of treatment; the scores after 3 and 6 months were
IL, USA). The quantitative variables are presented as the significantly lower than those before treatment (p < 0.05;
mean ± standard deviation and the categorical variables as Figure 2).
frequencies (and proportions). Student’s t-test and the chi- After combined treatment with AFCL and PRP, the
square test were used to compare the patient demographics. UNC4P and VSS scores were significantly lower than those
Two-way repeated measures analysis of variance and the after AFCL treatment alone. The differences between the
Mann–Whitney U test were used to compare the scores of UNC4P and VSS scores at the third and sixth months were
2 groups. All statistical tests were two-sided and p values statistically significant (p < 0.05). This suggests that the4 Burns & Trauma, 2021, Vol. 9, tkab016
Table 2. Improvement of UNC4P and VSS scores of hypertrophic scar patients after AFCL and AFCL+PRP treatments
AFCL AFCL+PRP
Pre-treatment First month Third month Sixth month Pre-treatment First month Third month Sixth month
UNC4P 7.68 ± 1.17 6.84 ± 1.27a 5.95 ± 0.55a 4.63 ± 1.09a 8.26 ± 1.22 6.52 ± 1.16b 4.68 ± 1.28b ,c 2.61 ± 1.29b ,c
Pliability 1.89 ± 0.31 1.89 ± 0.31 1.89 ± 0.31 1.68 ± 0.46a 2.00 ± 0.25 2.00 ± 0.25 1.90 ± 0.30 1.19 ± 0.40b ,c
Pruritus 2.00 ± 0.46 1.58 ± 0.59a 1.05 ± 0.51a 0.74 ± 0.44a 2.13 ± 0.55 1.23 ± 0.49b ,c 0.55 ± 0.56b ,c 0.16 ± 0.37b ,c
Pain 1.95 ± 0.60 1.53 ± 0.60a 1.21 ± 0.41a 1.00 ± 0.32a 2.06 ± 0.62 1.45 ± 0.50 0.90 ± 0.47b ,c 0.45 ± 0.50b ,c
1.84 ± 0.49 1.84 ± 0.49 1.74 ± 0.55 1.21 ± 0.61a 2.06 ± 0.44 1.84 ± 0.51 1.32 ± 0.47b ,c 0.80 ± 0.59b ,c
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Paraesthesia
VSS 10.89 ± 1.65 10.68 ± 1.66 9.89 ± 1.62a 8.16 ± 1.93a 11.74 ± 1.61 10.39 ± 1.31 8.45 ± 1.04b ,c 6.06 ± 1.44b ,c
Pigmentation 2.89 ± 0.45 3.00 ± 0 3.00 ± 0 2.68 ± 0.73 3.00 ± 0 3.00 ± 0 2.87 ± 0.49 2.16 ± 0.99b
Vascularity 3.21 ± 0.77 2.89 ± 0.97 2.37 ± 0.98a 1.79 ± 0.69a 3.61 ± 0.94 2.58 ± 0.84b 1.77 ± 0.61b ,c 1.06 ± 0.35b ,c
Height 2.00 ± 0.32 2.10 ± 0.45 2.16 ± 0.49 2.11 ± 0.55 2.19 ± 0.47 2.23 ± 0.49 1.87 ± 0.49b 1.68 ± 0.47b ,c
Pliability 2.79 ± 0.61 2.68 ± 0.65 2.37 ± 0.48a 1.58 ± 0.59a 2.94 ± 0.50 2.58 ± 0.55b 1.94 ± 0.35b ,c 1.16 ± 0.37b ,c
UNC4P University of North Carolina 4P Scar Scale, VSS Vancouver Scar Scale, AFCL ablative fractional CO2 laser, PRP platelet-rich plasma
a
p < 0.05 compared with pre-treatment value in AFCL group
b
p < 0.05 compared with pre-treatment value in AFCL+PRP group
c
p < 0.05 compared with the value of the AFCL group at the same time point
Figure 2. VSS values after AFCL and AFCL+PRP treatment. # p < 0.05 com-
Figure 1. UNC4P values after AFCL and AFCL+PRP treatment. # p < 0.05
pared with pre-treatment value in the AFCL group; † p < 0.05 compared with
compared with pre-treatment value in the AFCL group; † p < 0.05 compared
pre-treatment value in the AFCL+PRP group; § p < 0.05 compared with the
with pre-treatment value in the AFCL+PRP group; § p < 0.05 compared with
value of the AFCL group at the same time point. VSS Vancouver Scar Scale,
the value of the AFCL group at the same time point. UNC4P University of
AFCL ablative fractional CO2 laser, PRP platelet-rich plasma, M, month
North Carolina 4P Scar Scale, AFCL ablative fractional CO2 laser, PRP platelet-
rich plasma, M, month
After 6 months, the pliability, pain, pruritus and paraes-
thesia scores on the UNC4P in the AFCL group decreased
showed a downward trend after both treatments, and the by 0.21 ± 0.10, 0.95 ± 0.14, 1.26 ± 0.15 and 0.63 ± 0.14,
downward trend in the AFCL+PRP group was more obvi- respectively. The same scores on the UNC4P in the AFCL+PRP
ous than that in the AFCL group (difference, −1.68; 95% group were reduced by 0.81 ± 0.07, 1.61 ± 0.12, 1.97 ± 0.10
confidence interval (CI), −2.47, −0.80; p < 0.001; Figure 3a). and 1.26 ± 0.10, respectively, resulting in significantly lower
The VSS scores showed a similar downward trend (difference, scores than in the AFCL group (p < 0.05; Figure 4). During
−2.42; 95% CI, −3.68, −1.16; p < 0.001; Figure 3b). the same period, the pliability, vascularity, height and
From the results in Table 1, it can be seen that after pigmentation scores on the VSS in the AFCL group decreased
treatment with AFCL and AFCL+PRP, the UNC4P and VSS by 1.21 ± 0.14, 1.42 ± 0.16, −0.11 ± 0.11 and 0.21 ± 0.21,
scores were lower than before treatment, which means that respectively. The same scores on the VSS in the AFCL+PRP
the patients’ scars had improved. In order to analyse in detail group were reduced by 1.77 ± 0.10, 2.55 ± 0.17, 0.52 ± 0.09
the effect of these 2 treatments on scars, the sub-items of and 0.84 ± 0.18, respectively, resulting in significantly
the 2 assessments were analysed. The score at 6 months lower scores than in the AFCL group (p < 0.05; Figure 5).
of treatment minus the score before treatment was used to These results suggest that AFCL combined with PRP could
measure the effect of different treatment methods on the comprehensively improve scar formation.
UCN4P and VSS sub-items.Burns & Trauma, 2021, Vol. 9, tkab016 5
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Figure 3. Estimated marginal mean UNC4P (a) and VSS (b) scores by time. The decrease of UNC4P (a) and VSS (b) scores were observed in different treatment
groups; however, the UNC4P scores in AFCL+PRP group showed a more obvious downward trend than that in AFCL group (a), and the different downward
trend was statistically significant (difference, −1.68; 95% confidence interval (CI), −2.47, −0.80; p < 0.001). The VSS score showed a similar downward trend in
AFCL+PRP group and AFCL group (difference, −2.42; 95% CI, −3.68, −1.16; p < 0.001). UNC4P University of North Carolina 4P Scar Scale, VSS Vancouver Scar
Scale
Figure 4. Improvements of pliability (a), pain (b), pruritus (c) and paresthesia (d) as scored by the UNC4P before and after AFCL and AFCL+PRP treatment.
After 6 months treatment, the pliability (a), pain (b), pruritus (c) and paresthesia (d) scores on the UNC4P in the AFCL+PRP group were reduced by 0.81 ± 0.07,
1.61 ± 0.12, 1.97 ± 0.10 and 1.26 ± 0.10, respectively, resulting in significantly lower scores than that in the AFCL group (0.21 ± 0.10, 0.95 ± 0.14, 1.26 ± 0.15 and
0.63 ± 0.14, respectively; p < 0.05). ∗ p < 0.05, MannWhitney U test. UNC4P University of North Carolina 4P Scar Scale, AFCL ablative fractional CO2 laser, PRP
platelet-rich plasma6 Burns & Trauma, 2021, Vol. 9, tkab016
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Figure 5. Improvement of pliability (a), vascularity (b), height (c) and pigmentation (d) as scored by the VSS before and after AFCL and AFCL+PRP treatment.
After 6 months treatment, the pliability (a), vascularity (b), height (c) and pigmentation (d) scores on the VSS in the AFCL+PRP group decreased by 1.77 ± 0.10,
2.55 ± 0.17, 0.52 ± 0.09 and 0.84 ± 0.18, respectively, resulting in significantly lower scores than in the AFCL group (1.21 ± 0.14, 1.42 ± 0.16, −0.11 ± 0.11 and
0.21 ± 0.21, respectively; p < 0.05). ∗ p < 0.05, MannWhitney U test. VSS Vancouver Scar Scale, AFCL ablative fractional CO2 laser, PRP platelet-rich plasma
Discussion fractional CO2 laser treatment provides more improvement
There have been many reports on the application of PRP and in burn scars both clinically and histopathologically, espe-
AFCL in the treatment of scars, but most of these studies cially in the parameters of pliability and relief. There are also
were on acne scars [8–10]. The present study focused on many reports of the effectiveness of other treatment methods
the effect on hypertrophic scarring following a burn-related combined with PRP to treat hypertrophic> burn scars, such
injury. The results show that the combination of PRP and as autologous fat injection [15] and narrow-spectrum intense
AFCL significantly improved the quality of scars and exerted pulsed light [16].
a superior effect compared with the use of PRP alone. Although the VSS is a classic and commonly used scale,
PRP is a new treatment—a plasma therapy with a high it still has some shortcomings. In our study, the pigmentation
concentration of platelets, containing vascular endothelial of scars improved significantly after treatment in both groups,
growth factor, transforming growth factor, epidermal growth but it nonetheless appeared as pigmentation. Because the VSS
factor, fibroblast growth factor and so forth. It provides raw score for pigmentation only contains 3 grades, improvement
materials for tissue repair while recruiting stem cells to the of pigmentation cannot be reflected in this scale. When
local area of the skin lesions and promoting their proliferation evaluating the pigmentation of scars, researchers can make
to achieve the goals of skin tissue regeneration and control some improvements to the VSS or use other assessment scales
of excessive inflammatory reactions during the process of to compensate for this deficiency.
early wound repair [11]. The validity of laser therapy in the A recent study by Neinaa et al. [17] reported significant
treatment of hypertrophic scarring was verified again in our clinical improvement of post-acne scars treated with AFCL
study, as it previously has been in the literature [12,13]. Hult- combined with PRP, as evidenced by the significant reduction
man et al. also reported a significant decrease in the UNC4P in both the Clinique des Cicatrices d’Acné and Goodman and
and VSS scores of 147 burn patients after a single laser Baron’s qualitative scar scale scores with minimal adverse
treatment [6]. Therefore, we chose these 2 scales to measure effects. In that study, they found that AFCL-assisted delivery
the effect. A recent study [14] has shown that high-density of lyophilized growth factors, a new PRP preparation thatBurns & Trauma, 2021, Vol. 9, tkab016 7
is standardized in growth factor concentrations, reached a Abbreviations
higher degree of clinical improvement and patient satisfac- AFCL: ablative fractional CO2 laser; PRP: platelet-rich
tion. This is a huge technological advance that has great plasma; TBSA: total body surface area; UNC4P: University
prospects for development. of North Carolina 4P Scar Scale; VSS: Vancouver Scar Scale.
Fractional laser therapy creates precise, uniform columns
of tissue vaporization, which helps to facilitate drug delivery
past the epidermal barrier and even distribution of drugs in
the dermal layer [18].
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